The proposed project is designed to contribute to the development of a satisfactory conceptual framework within which to view general relationships of dose to effect. Several sub-projects are involved: (a) The mechanicsm by which anesthetics potentiat the effect of neuromuscular blocking agents will be examined by determining whether anesthetics alter the binding properties of the receptor at the neuromuscular junction. (b) A method for objective statistical analysis of concentration-time curves will be developed (pharmacokinetics). (c) The extent and kinetics of onset and offset of phase II neuromuscular block will be determined. (d) An attempt will be made to develop a generalized model for the drug-receptor reaction. Particular consideration will be given to fitting in both the phenomenon of desensitization and of cooperativity. (e) The affinity of neuromuscular blocking agents for the receptors of guinea pigs with myasthenia gravis will be measured with a view to determining whether the receptor is altered in these animals.